Silicic acid condensates having a low degree of cross-linking in a polymer matrix

ABSTRACT

A material or biomaterial comprising silicic acid condensates having a low degree of cross-linking, and methods for its production are subject-matter of the invention. A method for the production of silicic acid structures having a low degree of cross-linking is disclosed, wherein a sol is produced, wherein further condensation is prevented when specific cross-linking of the silicic acid is reached, wherein, preferably, structures having a size of 0.5-1000 nm are produced, e.g. polyhedral structures or aggregates of the same. Further condensation can be prevented by means of mixing with a polymer. In one embodiment, this comprises nano-structured, silicon dioxide (SiO 2 ) having a low degree of cross-linking that is embedded in a polymer matrix. The material can be used in medicine for therapeutic purposes, and can enter into direct contact with biological tissue of the body in this connection. This material herein enters into chemical, physical, and biological interactions with the corresponding biological systems. It can herein be decomposed, and can act as a supplier for the silicic acid required for metabolism. Furthermore, it can have a supportive or shielding effect. It can be present as a granulate, microparticles, fiber, and as a woven or nonwoven fabric produced therefrom, or as a layer on implants or wound dressings. The material can be used as a medical device or as a nutritional supplement.

A material or biomaterial comprising silicic acid condensates having alow degree of cross-linking, and methods of producing the same aresubject matter of the present invention. A method for the production ofsilicic acid structures having a low degree of cross-linking isdisclosed, in which a sol is produced, wherein further condensation isprevented once a specific degree of cross-linking of the silicic acid isreached, wherein, preferably, structures having a size of 0.5-1000 nmare produced, for example polyhedral structures or aggregates thereof.Further condensation can be prevented by mixing with a polymer. In oneembodiment, this comprises nanostructured, silicon dioxide (SiO₂) havinga low degree of cross-linking that is embedded in a polymer matrix. Thematerial can be used in medicine for therapeutic purposes, and, in thisconnection, can enter into direct contact with biological tissue of thebody. When this happens, this material enters into chemical, physicaland biological interactions with the corresponding biological systems.In this connection, it can be decomposed and can act as a supplier ofthe silicic acid needed in metabolism. Furthermore, it can have asupportive or shielding effect. It can be present as a granulate,microparticles, fiber, and woven or nonwoven fabric produced therefrom,or as a layer on implants or wound dressings. The material can be usedas a medical device or as a nutritional supplement.

Since the 70s of the past century, it is known that silicon is animportant trace element for building bones and collagen (see, forexample, M. Carlisle; Silicon: An Essential Element for the Chick;Science 10 Nov. 1972: Vol. 178. no. 4061, pp. 619-621). The precisebiochemical processes continue to be unknown. In the metabolism, siliconprimarily occurs as silicon dioxide. It is also not known in whatstructure the silicon dioxide best participates in the metabolism.Silicon dioxide occurs as a crystalline compound (e.g. quartz,cristobalite), as glass and as an amorphous substance. In crystal and inglass, the silicon is determined by almost complete cross-linking of theSiO_(4/2) tetrahedrals. Amorphous silicon dioxide with the significantrepresentative of silica gel, in contrast, has a network that is notcontinuous and that is characterized by more or less internal surfacewith open bonds (mostly SiOH).

With regard to degradation of silicon dioxide, the solubility of silicondioxide in water in the range of physiological pH is of interest. Foramorphous SiO₂ at pH 7, it lies at approximately 150 ppm. In contactwith living tissue, dissolution takes place more quickly than in buffersolution pH 7.4. The reason for this is unknown (Iler, The Chemistry ofSilica, 1979, John Wiley & Sons).

For wound dressings, in patent US005741509A, mixing of silicone mediumwith “fumed silica” is described. “Fumed silica” consists of non-porousSiO₂ particles having a density of 2.2 g/cm³ and a size between 5 and 50nm (Wikipedia). The density, which is identical to that of silica glass,just like the absence of porosity, shows that these are completelycross-linked SiO₂ structures.

In patent US2004/0235574A1, mixing of silicone medium with “fumedsilica” is described, wherein additionally, substances having anantibacterial effect are added.

Patent U.S. Pat. No. 7,074,981 B2 describes a wound dressing in which anabsorbent or an adsorbent in the form of silica gel is used. Anabsorbent or an adsorbent composed of silica gel is, according to thestate of the art, a xerogel, which is generally produced from sodiumsilicate solution, where cross-linking of the SiO₂ structures that istypical for a xerogel takes place. (Under Wikipedia “Adsorption”:“Silica gel is a chemically inert, nontoxic, polar and dimensionallystable (<400° C. or 750° F.) amorphous form of SiO₂. It is prepared bythe reaction between sodium silicate and acetic acid, which is followedby a series of after-treatment processes such as aging, pickling, etc.These after-treatment methods result in various pore sizedistributions.”)

Patent DE 196 09 551 C1 concerns itself with biologically degradablefibers, composed of SiO₂, among other things, their production and theiruse as reinforcement fibers. Here, the production of a sol that can bespun is described. The method described and the application describedare based on a diploma thesis by Monika Kursawe from 1995. The thesis inturn is based on the original synthesis instructions of Sakka from 1982(S. Sakka, K. Kamiya; J. Non-Cryst. Solids 48, 1982 31). Sakka describesa method in which gel threads are spun, from which glass fibers are thenproduced in a later step. The starting material istetraethylorthosilicate (TEOS), wherein a sol that can be spun isproduced by means of hydrolysis and condensation. Sakka already showsthat only a limited range in the composition (TEOS, H₂O, solvent(generally ethanol) and catalyst) leads to sols that can be spun, as aresult of the thixotropic properties of the sols. In particular, themolar ratio of water to TEOS must lie around r_(w)2.

In the dissertation “Development of a method for the production ofdegradable silica gel fibers for medical technology” (Monika Kursawe1999), a further development of the 1995 thesis of Kursawe, it is statedthat the most important difference between the method described in herthesis and the method of Sakka is that after condensation, solmaturation was introduced, and that nitric acid was used as a catalystinstead of hydrochloric acid. In the dissertation, the method is thenoptimized in such a manner that the production of high-quality silicagel fibers in larger amounts can take place. The process is based on theslightly modified synthesis instruction of Sakka described in thethesis.

Patent DE 37 80 954 T2 describes a method of silicon dioxide glassfibers, wherein, here, too, the basic method of Sakka was modified.

Patent DE 10 2007 061 873 A1 describes the production of a silica solmaterial and its use as a biologically resorbable material. Patent DE19609551C1 is referred to as prior art. As a distinction from thispatent, it is stated that here that the fibers do not achieve optimalresults in cytotoxicity tests after spinning; the causes for this can bemany and are not related to the essential method steps. The seconddistinction, that a “solid phase” is formed according to DE 10 2007 061873 A1, which brings about compulsory filtering of the sol, is also notbrought into relation with the essential method steps. The main claim 1of patent DE 10 2007 061 873 A1 essentially reproduces the productioninstructions that M. Kusawe describes in her dissertation (1999) andthat were also published in her thesis in 1995. M. Kusawe divides theproduction of sol that can be spun into “hydrolysis,” “condensation,”and “maturation.” According to Kusawe, “condensation” is characterizedin that ethanol is withdrawn from the sol. This corresponds to claim 1b) of the patent DE 10 2007 061 873 A1. In Kusawe, “maturation” takesplace at 5° C., in her standard approach. This in turn corresponds toclaims 1 c) and 1 d). In the example of the patent DE 10 2007 061 873A1, maturation is conducted at 4° C. In terms of the other essentiallyparameters, as well, the example corresponds to the standard approach ofKusawe (e.g. molar ratio of water/TEOS 1.75, in Kusawe 1.8). The methodsfor the production of sols that can be spun of patents DE 196 09 551 C1and DE 10 2007 061 873 A1, in terms of their essential steps, do not gobeyond the level of knowledge of the thesis of Kusawe from 1995. Thethesis is also strongly based on the level of knowledge of Sakka from1982 (S. Sakka, K. Kamiya; J. Non-Cryst. Solids 48, 1982 31).

It is the task of the present invention to optimize the structure ofsilicic acid condensation products in such a manner that controlleddegradation can take place in in vivo application, and that thesesilicic acid condensation products can be present in specificapplication forms such as granulate, microparticles, fibers, or aslayers on implants or wound dressings. Production methods are to be madeavailable for this purpose.

According to the invention, this task is accomplished in that thecondensation of the silicic acid is controlled in aqueous or inalcoholic solution in such a manner that defined polyhedral structuresare formed and that these polyhedral structures are maintained duringthe subsequent method steps such as, for example, removal of thesolvent. The goal is to produce silicic acid structures having a lowdegree of cross-linking, which are characterized in that they are notintegrated into a continuous network like the fused silica network. Inthis connection, the lowest degree of cross-linking is represented by apolyhedral composed of SiO₂ tetrahedrals, where five-, six- andseven-rings form a spatial structure of approximately 0.5 nm diameter.Such structures are described in: B. Himmel, Th. Gerber and H. Burger:WAXS- and SAXS-investigations of structure formation in alcoholic SiO₂solutions, Journal of Non-Crystalline Solids, Amsterdam, 119(1990)1-13;B. Himmel, Th. Gerber and H. Burger: X-ray diffraction investigations ofsilica gel structures, Journal of Non-Crystalline Solids, Amsterdam,91(1987)122-136; B. Himmel, Th. Gerber, W. Heyer and W. Blau: X-raydiffraction analysis of SiO₂ structure, Journal of Material Science,Chapman and Hall Ltd., London, 22(1987)1374-1378; Th. Gerber and B.Himmel: The structure of silica glass in dependence on the fictivetemperature, Journal of Non-Crystalline Solids, Amsterdam,92(1987)407-417; Th. Gerber and B. Himmel: The structure of silicaglass, Journal of Non-Crystalline Solids, Amsterdam, 83(1986)324-334; B.Himmel, Th. Gerber and H.-G. Neumann: X-ray diffraction investigationsof differently prepared amorphous silicas, Physica Status Solidi (a),88(1985) K127-K130).

One starting material for the production of silicic acid condensationproducts is tetraethyl-orthosilicate (TEOS). Silicic acid is formed withwater, in the presence of a catalyst, wherein the molar ratio ofwater/TEOS must be at least 4 in order to achieve complete hydrolysis atthe starting point. The mono-silicic acid that is formed condenses andforms polyhedral structures of approximately 0.5 nm-1 nm, called primaryparticles, which then form fractal clusters in a cluster-clusteraggregation. These clusters grow as a result of the aggregation process,and, at a specific size of the clusters, gel formation occurs. In otherwords, the clusters fill the container as a result of their packing orby means of the percolation network that has formed (Th. Gerber, B.Himmel and C. Hübert: WAXS and SAXS investigation of structure formationof gels from sodium water glass, Journal of Non-Crystalline Solids,(1994) Vol. 175, p. 160-168 and B. Knoblich, Th. Gerber. C. F. Brinkerand G. W. Scherer describe gel formation in an extra chapter in“Sol-gel-science: The physics and chemistry of sol-gel processing”(Academic Press; San Diego; 1990). Gel formation is characterized by anextreme increase in viscosity.

These or analogous structures can be produced on the basis of sodiumsilicate solution. In this connection, the sodium ions are preferablyremoved from the solution using an ion exchanger. The remaining silicicacid here is then already present as a condensation product. These arepolyhedral structures having a size of approximately 0.5 nm, once againcalled primary particles, which then form fractal clusters as a functionof the pH, by means of aggregation, which in turn lead to gel formation(B. Knoblich, Th. Gerber: Aggregation in SiO₂ sols from sodium silicatesolutions, Journal of Non-Crystalline Solids 283 (2001) 109-113).

The aggregation clusters (solid scaffolding, metal oxide) of the alcogel(solvent, alcohol) or hydrogel (solvent, water) are destroyed duringdrying by the capillary forces that are in effect and by thecondensation of the internal surface that takes place(2Si_(surface)-OH→Si_(bulk)-O-M_(bulk)+H₂O). A xerogel is formed, theinternal surface of which lies, for example, in the case of SiO₂, in therange of 25-700 m²/g, and the density of which lies in the range above1.0 g/cm³. The defined polyhedral structures in the primary particlescross-link during drying. A continuous network is formed having thegreat internal surface described above. Cross-linking of the silicondioxide is increased.

In the production of aerogels, this process is prevented. For this,there are two fundamentally different paths according to the state ofthe art.

For one thing, super-critical drying methods are used. In this way, theeffect of the capillary forces is hindered, because the liquid/gas phasetransition is circumvented by a corresponding temperature/pressureregime. Herein, alcohols (methanol, ethanol, propanol) or liquid CO₂ areused as solvents, which must replace the original solvent, mostly H₂O,by means of exchange methods (S. S. Kistler, Phys. Chem. 36 (1932)52-64, EP 171722; DE 1811353; U.S. Pat. No. 3,672,833; DE 39 24 244 Al;PCT/EP94/02822). The methods are very costly due to the autoclaves thatare used.

On the other hand, there are methods according to the state of the artthat allow sub-critical drying of aerogels. The core point of the methodaccording to PCT/US94/05105 is modification of the contact angle betweensolvent and solid scaffolding. In this way, the capillary pressure isreduced and the structure of the moist gel is almost maintained. Thecontact angle is achieved by means of modification of the internalsurface of the solid scaffolding in the moist gel. For this purpose, areaction of the internal surface with R_(X)SiX_(Y) takes place. R is anorganic group and X is a halogen. In this method, multiple solventexchanges are required. In patent DE 19538333 A1, modification of theinternal surface of the moist gel is implemented with Si_(surface)O-Z,wherein Z is any desired group that is supposed to prevent condensationof the internal surface during drying.

The methods used for the production of aerogels are not utilized withinthe scope of the present invention; in particular, gel formation doesnot occur.

It is the task of the present invention to produce materials having adefined degree of cross-linking of the silicic acid. From this, productssuch as microparticles, fibers or layers can be produced.

According to the invention, this task is accomplished in that furthercondensation is prevented in a sol once specific degrees ofcross-linking of the silicic acid have been reached, particularly oncethe desired size of the silica gel clusters or the sol particles hasbeen achieved by means of condensation, wherein the desired size of thesilica gel clusters or sol particles preferably lies in the range ofapproximately 0.5 nm up to approximately 1000 nm, more preferably from0.5 nm to 20 nm, more preferably from 0.5 nm to 10 nm, from 0.5 nm to 5nm, from 0.5 nm to 4 nm, from 0.5 nm to 3 nm, from 0.5 nm to 2 nm orfrom 0.5 nm to 1 nm.

This happens in that a solution, particularly an aqueous solution of asoluble polymer, preferably polyvinylpyrrolidone (PVP), is added. Aparticularly preferred PVP is K90. Preferably, mixing takes place untilthe silicic acid structures are homogeneously distributed in thepolymer. In particular, homogenization can be undertaken with anultrasound homogenizer, for example. Mixing with a stirrer having highshear forces has equally proven to be effective. In one embodiment, thepH is adjusted, after mixing, to approximately 6-8, particularlyapproximately pH 7 to approximately pH 7.4.

Surprisingly, in this connection, no precipitation of the silicic acidtakes place. A gel is formed in which the SiO₂ condensation products andthe molecules of the polymer (e.g. PVP) are homogeneously distributed.

This gel can be used, for example, in ointments or creams for woundtreatment, for treatment of scars, or for cosmetic applications.

During drying, preferably during freeze-drying of the mixture, polymerand silicic acid polyhedral remain homogeneously distributed (see FIG.1). During use as a wound dressing, the polymer can go into solutionagain, and thereby release the silicic acid polyhedrals.

Solutions capable of being spun can also be produced from apolymer/SiO₂/solvent mixture, wherein the solvent preferably is water.For this purpose, the ratio of polymer (preferably PVP), SiO₂ andsolvent preferably is selected so that after mixing, the viscosity liesin the range of approximately 0.7-1.3 Pas, particularly at approximately1 Pas. The solution can be pressed through nozzles immediately. In aspinning tower, the threads can dry in a tempered gas stream.

In this embodiment, in particular, a method for producing silicic acidstructures having a low degree of cross-linking in a polymer matrix issubject matter of the invention, wherein:

a) a SiO₂ sol is produced in a solvent, wherein the sol particlespreferably have a size of 0.5 nm to 4 nm,

b) a solution of a polymer in a solvent is produced,

c) the solution and the sol are homogeneously mixed.

In this connection, the solvent can be water or alcohol or a mixture ofwater and alcohol, wherein the alcohol is preferably ethanol.

In one embodiment of the invention, the pH of the sol is adjusted instep a) to the range of 6 to 8. In step b) the pH of the polymersolution can be adjusted to the range of 6 to 8.

In another embodiment of the invention, the sol is produced withoutadjusting the pH. The pH of the sol then preferably lies atapproximately pH 2. The polymer solution for step b) can also beproduced without adjusting the pH, wherein the pH of this solution thenpreferably lies, for example, in the case of PVP, at approximately 4. Inthis embodiment, the pH is preferably adjusted to 6-8 after mixing instep c), in particular to pH 7.

Mixing is in particular carried out until a homogeneous distribution ofthe silicic acid structures in the polymer has been reached. Forexample, mixing for approximately 6 min while stirring at 1000 rpm ispossible.

Preferably, in the method according to the invention, SiO₂ and polymerare present in a mass ratio of 0.5/99.5 (SiO₂/polymer) to 50/50 (in stepc) or in the end product).

Preferably, in the method according to the invention, the polymer ispolyvinylpyrrolidone.

Preferably, in this method, the mixture from step c) is dried. Themixture can be cast into a mold and freeze-dried.

Preferably, so much solvent is removed from the mixture that theviscosity preferably lies in the range of 0.5 Pas to 1 Pas. As a result,threads can be spun that preferably are dried in a tempered gas stream.A nonwoven or woven fabric can be produced from these threads.

Within the scope of this method, the degree of cross-linking of thepolymer, e.g. of the PVP, can be increased according to known methods,preferably by means of gamma irradiation.

A material that can be produced with a method according to the inventionis also subject matter of the invention.

A material that can also be referred to as a biomaterial, and that iscomposed of SiO₂ structures, particularly polyhedral structures, whichhave a size of preferably 0.5 nm to 4 nm, and which are homogeneouslydistributed in a polymer matrix, is also subject matter of theinvention. Preferably, the material is a hydrogel composed of SiO₂structures, which preferably have a size of 0.5 nm to 4 nm, and which ismade of a water-soluble polymer or comprises a water-soluble polymer,wherein polymer and SiO₂ structures are homogeneously distributed. Thesilicic acid structures having a low degree of cross-linking are, inparticular, polyhedral structures or aggregates thereof. Aggregates ofpolyhedral structures are composed of polyhedral structures.

Preferably, in this material, SiO₂ and polymer are present in a massratio of 0.5/99.5 (SiO₂/polymer) to 50/50.

Preferably, in this material the polymer is polyvinylpyrrolidone, e.g.K90.

Preferably, this material is present as threads, which preferably form anonwoven or woven fabric, as a film or as a sponge.

In one embodiment, this material (biomaterial), together with granulatesthat can be used or are used as bone replacement material, form a massfor filling bone defects (putty). Commercially available granulates canbe used.

Such granulates are disclosed, for example, in WO 2004/103421 and EP 1624 904. Nanobone (Artoss GmbH, Rostock, Germany) can be used, forexample. Particularly preferred are highly porous bone replacementmaterial granulates, particularly granulates on the basis of calciumphosphate, such as crystalline calcium phosphate that is embedded in asilicon dioxide xerogel matrix. Such granulates on the basis of calciumphosphate can particularly be obtained by means of production of thecalcium phosphate by way of a precipitation reaction, in which thesolution with the precipitated calcium phosphate is homogenized bystirring, a highly concentrated silicic acid solution is added, themixture is fixed by means of the gel formation that subsequently occurs,and the mixture is transformed into a xerogel matrix by removing thesolvent, wherein the calcium phosphate crystallites that lie in thexerogel matrix have a size of about 10 nm to about 2000 nm, and thegranulate grains have a size of 1 μm to 1000 μm, and the silicon dioxidecomponent lies in the range of 2 to 80 wt.-%, preferably in the range of4 to 50 wt.-%, with reference to the total mass of the granulate grains.Furthermore, bone replacement materials in granulate form having abovine origin (e.g. BioOss from the Geistlich company) or hydroxylapatite ceramics (e.g. sintered hydroxyl apatite ceramics, such asCerabone—aap Implantate AG, for example) can be used within the scope ofthe present invention. However, it must be taken into consideration thatin the case of a putty based on water, no water-soluble granulates (e.g.β-TCP) can be used.

Use of the material for medical devices, particularly for those thathave a supporting or shielding function and/or simultaneously serve as asupplier for the silicon dioxide that supports tissue regeneration, isalso subject matter of the invention. Within the scope of the invention,the term medical device is used interchangeably with medical orpharmaceutical composition or medicament, because classification dependson national law, but does not change the substance of the invention.

An object of the invention is also use of the material as an ointment orcream, particularly for the treatment of wounds, scars, or for cosmeticapplications.

An object of the invention is also a medical device that comprises thematerial according to the invention.

The present invention furthermore relates to methods for the productionof a formable bone replacement material (putty), wherein a) a granulatethat can be used as a bone replacement material is moistened with anaqueous solution, and b) the granulate that can be used as a bonereplacement material is mixed with a biomaterial produced as describedabove. Granulates that can be used within the scope of this methodcomprise the granulates disclosed above.

In a particular embodiment, the mixture produced in step b) isfreeze-dried, so that the user (for example a surgeon) can add anantibiotic solution (e.g. a gentamicin solution) to the sponge thatformed, and thereby obtains a formable bone replacement materialcomprising antibiotics.

In another preferred embodiment, the formable bone replacement material(putty) is subjected to gamma irradiation at preferably 25-40 kGray,thereby forming elastic blocks.

Furthermore, a formable bone replacement material (putty) comprising agranulate that can be used as a bone replacement material and abiomaterial that has been produced as described above, is subject matterof the invention. Preferably, the formable bone replacement material(putty) is produced according to the methods described above.

The invention is explained and illustrated in the following examples,but not restricted by these in terms of its scope. Publications cited inthis application are completely incorporated herein by reference.

FIGURE LEGENDS

FIG. 1 shows, in various enlargements, scanning electron microscopyimages of the sponge produced in Example 1 from polyvinylpyrrolidone andSiO₂ nanoparticles. A: scale=200 μm, B: scale=40 μm, C: scale=9 μm.

EXAMPLES Example 1

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 6% SiO₂ content isformed. 200 g of this sol are homogeneously mixed with 200 g of atwelve-percent PVP solution. For this purpose, ultrasound homogenizationis used. Subsequently, the pH is adjusted to 7.4 with NaOH solution. Thegel is placed in molds, for example with a size of 100 mm×100 mm×8 mm,and freeze-dried. Scanning electron microscopy images are shown in FIG.1.

Example 2 Water-Soluble Nonwoven Fabric for Covering Wounds

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 0.66% SiO₂ content isformed. 200 g of this sol are homogeneously mixed with 200 g of anaqueous 1.34% PVP K 90 solution (PVP—polyvinylpyrrolidone). For mixing,a stirrer is used at 1000 rpm. Subsequently, the pH is adjusted to7.4±0.5 with NaOH solution. The gel is placed in molds with, forexample, a size of 100 mm×100 mm×8 mm, and freeze-dried. A nonwovenfabric for wound covering is formed.

Example 3 Water-Insoluble Nonwoven Fabric for Wound Covering

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 0.66% SiO₂ content isformed. 200 g of this sol are homogeneously mixed with 200 g of anaqueous 1.34% PVP K 90 solution (PVP—polyvinylpyrrolidone). For mixing,a stirrer is used at 1000 rpm. Subsequently, the pH is adjusted to7.4±0.5 with NaOH solution. The gel is placed in molds with, forexample, a size of 100 mm×100 mm×8 mm, and freeze-dried. Afterward, thenonwoven fabric that has formed is exposed to saturated steam until ithas absorbed 10% of its weight in water (swelling). Subsequent gammairradiation (25-40 KGray) ensures cross-linking of the PVP in thenonwoven fabric. A nonwoven fabric for wound covering is formed.

Example 4 Gel-Like Wound Covering

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 6% SiO₂ content isformed. 200 g of this sol are homogeneously mixed with 200 g of anaqueous 12% PVP K 90solution (PVP—polyvinylpyrrolidone). For mixing, astirrer is used at 1000 rpm. Subsequently, the pH is adjusted to 7.4±0.5with NaOH solution. The gel is placed in molds with, for example, a sizeof 100 mm×100 mm×8 mm, and subjected to gamma irradiation of 25-40kGray. A gel-like moist wound covering is formed.

Example 5 Bone Replacement Material Putty

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 6% SiO₂ content isformed. 50 g of this sol are homogeneously mixed with 50 g of an aqueous12% PVP K 90 solution (PVP—polyvinylpyrrolidone). For mixing, a stirreris used at 1000 rpm. 62 g of a highly porous bone replacement materialgranulate (produced according to patent EP 1 624 904) are mixed with asmuch water that the internal pores are filled (in this case with 44 gwater). The silica/PVP mixture and the moist granulate are homogeneouslymixed. Subsequently, the pH is adjusted to 7.4±0.5 with NaOH solution.The mass is filled into typical applicators for bone replacement andsterilized in an autoclave.

Example 6

Bone replacement material putty for mixing with commercially availableantibiotic solutions With a cation exchanger (e.g. LEWATIT®), the sodiumions are removed from sodium silicate solution having a SiO₂ content of7%. A sol with a pH of approximately 2.4 is formed. After adetermination of the content of solids, water is added until a solhaving a 6% SiO₂ content is formed. 50 g of this sol are homogeneouslymixed with 50 g of an aqueous 12% PVP K 90 solution(PVP—polyvinylpyrrolidone). For mixing, a stirrer is used at 1000 rpm.62 g of a highly porous bone replacement material granulate (produced asdescribed in European Patent EP 1 624 904) are mixed with as much waterthat the internal pores are filled (in this case with 44 g water). Thesilica/PVP mixture and the moist granulate are homogeneously mixed.Subsequently, the pH is adjusted to 7.4±0.5 with NaOH solution.Cylinders are formed from the mass (10 mm diameter, 30 mm length). Thesecylinders are freeze-dried. Sponge-like dry elements are formed, whichare introduced into applicators having an inside diameter of 10 mm.Steam-tight packaging in commercially available aluminum peel bags andgamma sterilization take place subsequently. For use, as much antibioticsolution is added to the sponge-like elements in the applicator thatthere is no air in the applicator (e.g. 1.5 ml Gentamicin-ratiopharm® 40SF injection solution). The sponge-like cylinder swells and yields akneadable mass (putty) for filling of bone defects.

Example 7 Elastic Molded Element of Bone Replacement Material

With a cation exchanger (e.g. LEWATIT®), the sodium ions are removedfrom sodium silicate solution having a SiO₂ content of 7%. A sol with apH of approximately 2.4 is formed. After a determination of the contentof solids, water is added until a sol having a 6% SiO₂ content isformed. 50 g of this sol are homogeneously mixed with 50 g of an aqueous12% PVP K 90 solution (PVP—polyvinylpyrrolidone). For mixing, a stirreris used at 1000 rpm. 62 g of a highly porous bone replacement materialgranulate (produced as described in European Patent EP 1 624 904) aremixed with as much water that the internal pores are filled (in thiscase with 44 g water). The silica/PVP mixture and the moist granulateare homogeneously mixed. Subsequently, the pH is adjusted to 7.4±0.5with NaOH solution. The mass is placed into molds (blister packs 15×10×5mm³). Steam-tight packaging in commercially available aluminum peel bagsand gamma sterilization at preferably 25-40 kGray follow. Elastic blocksthat are used for bone augmentation form.

1. A method for the production of silicic acid structures having a lowdegree of cross-linking in a polymer matrix, comprising a) producing aSiO₂ sol in a solvent, wherein the sol particles preferably have a sizeof 0.5 nm to 1000 nm, particularly of 0.5 nm to 4 nm, b) producing asolution of a polymer in a solvent, c) mixing the solution and the solhomogeneously.
 2. A method for the production of silicic acid structureshaving a low degree of cross-linking in a polymer matrix, preferablyaccording to claim 1, comprising producing a sol, and further preventingcondensation in the sol by adding a solution of a soluble polymer oncespecific degrees of cross-linking of the silicic acid have been reached,wherein preferably silicic acid structures having a size of 0.5-1000 nmin a polymer matrix are produced.
 3. A method for the production ofsilicic acid structures having a low degree of cross-linking, accordingto claim 2, comprising controlling the condensation of the silicic acidin aqueous or in alcoholic solution in such a manner that definedsilicic acid structures are formed by adding a solution of a solublepolymer once specific degrees of cross-linking of the silicic acid havebeen reached, and wherein these polyhedral structures are maintainedduring the subsequent method steps such as, for example, removal of thesolvent, thus producing silicic acid structures having a low degree ofcross-linking, which are not integrated in a continuous network, whereinpreferably, silicic acid structures having a size of 0.5-1000 nm in apolymer matrix are produced, and/or wherein the silicic acid structurespreferably are polyhedral structures, more preferably, essentially SiO₂tetrahedrals, wherein five-, six- and/or seven-rings form a spatialstructure of approximately 0.5 nm diameter.
 4. The method according toclaim 1, wherein the solvent is water or alcohol or a mixture of waterand alcohol.
 5. The method according to claim 1, wherein SiO₂ andpolymer are present in a mass ratio of 0.5/99.5 (SiO₂/polymer) to 50/50.6. The method according to claim 1, wherein the polymer ispolyvinylpyrrolidone (PVP), preferably polyvinylpyrrolidone K90.
 7. Themethod according to claim 1, comprising drying the mixture produced instep c).
 8. The method according to claim 1, comprising pouring themixture produced in step c) into a mold and freeze-drying it.
 9. Themethod according to claim 1, comprising removing solvent from themixture produced in step c), preferably so much that the viscosity liesin the range from 0.5 Pas to 1 Pas, and/or comprising spinning threadsthat preferably are dried in a tempered gas stream, wherein preferably anonwoven fabric or a woven fabric is produced from the threads.
 10. Themethod according to claim 1, comprising increasing the degree ofcross-linking of the polymer, preferably the PVP, preferably by means ofgamma irradiation.
 11. The method according to claim 1, wherein the solis produced by means of hydrolysis of tetraethylorthosilicate (TEOS),wherein preferably a r_(w) value (molar ratio of water to TEOS) of 4 isused, or wherein the sol is produced by means of ion exchange fromsodium silicate solution.
 12. The method according to claim 1,comprising adjusting the pH of the mixture of sol and polymer solutionproduced in step c) to approximately 6-8.
 13. A biomaterial, obtainableaccording to a method according to claim 1, which is composed of silicagel structures having a low degree of cross-linking, which structurespreferably have a size of 0.5 nm to 1000 nm, more preferably of 0.5 nmto 4 nm, and which are distributed in a polymer matrix, preferablypolyvinylpyrrolidone.
 14. A biomaterial, preferably according to claim13, composed of SiO₂ structures, preferably polyhedral structures havinga size of 0.5 nm to 4 nm, and which are homogeneously distributed in apolymer matrix.
 15. The biomaterial according to claim 13, which is ahydrogel composed of SiO₂ polyhedral structures, which have a size of0.5 nm to 4 nm, and a water-soluble polymer, wherein polymer and SiO₂polyhedral structures are homogeneously distributed.
 16. The biomaterialaccording to claim 13, wherein SiO₂ and polymer are present in a massratio of 0.5/99.5 (SiO₂/polymer) to 50/50.
 17. The biomaterial accordingto claim 13, wherein the polymer is polyvinylpyrrolidone, preferablypolyvinylpyrrolidone K90.
 18. The biomaterial according to claim 13,which is present as threads that preferably form a nonwoven or wovenfabric, as a film, or as a sponge.
 19. The biomaterial according toclaim 13, which, together with granulates that can be used as bonereplacement material, forms a mass for filling of bone defects (putty).20. The biomaterial according to claim 13 for use as a medical devicehaving a supporting or shielding function, and which by means ofdegradation preferably can simultaneously serve as a supplier for thesilicon dioxide that supports tissue regeneration.
 21. The biomaterialaccording to claim 13 for use for the treatment of wounds or scars orfor cosmetic applications, particularly as an ointment or cream.
 22. Amedical device or a nutritional supplement comprising the biomaterialaccording to claim
 13. 23. A method for the production of a formablebone replacement material (putty), comprising a) moistening a granulatethat can be used as a bone replacement material with an aqueoussolution, and b) mixing the granulate that can be used as bonereplacement material with a biomaterial according to claim
 13. 24. Themethod according to claim 23, wherein the granulate that can be used asa bone replacement material comprises porous material.
 25. The methodaccording to claim 23, wherein the granulate that can be used as a bonereplacement material comprises a calcium phosphate.
 26. The methodaccording to claim 23, wherein the granulate that can be used as a bonereplacement material is of bovine origin.
 27. The method according toclaim 23, wherein the granulate that can be used as a bone replacementmaterial comprises hydroxyl apatite ceramic.
 28. The method according toclaim 23, comprising freeze-drying the formable bone replacementmaterial (putty).
 29. The method according to claim 23, comprisingsubjecting the formable bone replacement material (putty) to gammairradiation at preferably 25-40 kGray.
 30. A formable bone replacementmaterial (putty), comprising a granulate that can be used as a bonereplacement material and a biomaterial according to claim 13.